pneumolysin

Pneumolysin (PLY) is a cholesterol-dependent cytolysin produced by Streptococcus pneumoniae. It is a pore-forming toxin released during autolysis of the bacterium and, in some contexts, secreted in small amounts. PLY binds to cholesterol in host cell membranes, oligomerizes, and inserts transmembrane pores, leading to lysis of many cell types including epithelial cells, leukocytes, and erythrocytes. The pore formation disrupts membrane integrity, alters ion gradients, and can trigger cell death by necrosis or apoptosis. In addition to direct cytotoxicity, pneumolysin can provoke inflammation by activating complement, stimulating cytokine release (e.g., TNF-α, IL-1β), and modulating immune responses, thereby contributing to tissue damage and disease severity.

Pathogenesis: Pneumolysin contributes to pulmonary damage in pneumonia, disrupts the blood–brain barrier in meningitis, and participates in middle-ear pathology during otitis media. It is a key virulence factor of S. pneumoniae; strains lacking ply tend to be less virulent in animal models.

Structure and genetics: The ply gene encodes a ~53-kDa toxin. Pneumolysin lacks a classical signal peptide and is released mainly upon bacterial lysis. There are natural variants with different cytolytic activity.

Clinical relevance and research: Detoxified pneumolysin derivatives (for example, PlyD-type toxoids) are being explored as vaccine antigens or adjuvants. Therapeutic approaches aim to inhibit cholesterol binding or pore formation to reduce tissue damage during infection.